bioRxiv最新文献_第10页

Deletion of endocannabinoid synthesizing enzyme DAGLα from cerebellar Purkinje cells decreases social preference and elevates anxiety 小脑浦肯野细胞中内源性大麻素合成酶 DAGLα 的缺失会降低社交偏好并加剧焦虑

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.08.607068

Gabriella Smith, Kathleen McCoy, Gonzalo Viana Di Prisco, Alexander Kuklish, Emma Grant, Mayil Bhat, Sachin Patel, Ken Mackie, Brady K. Atwood, A. Kalinovsky

{"title":"Deletion of endocannabinoid synthesizing enzyme DAGLα from cerebellar Purkinje cells decreases social preference and elevates anxiety","authors":"Gabriella Smith, Kathleen McCoy, Gonzalo Viana Di Prisco, Alexander Kuklish, Emma Grant, Mayil Bhat, Sachin Patel, Ken Mackie, Brady K. Atwood, A. Kalinovsky","doi":"10.1101/2024.08.08.607068","DOIUrl":"https://doi.org/10.1101/2024.08.08.607068","url":null,"abstract":"The endocannabinoid (eCB) signaling system is robustly expressed in the cerebellum starting from the embryonic developmental stages to adulthood. There it plays a key role in regulating cerebellar synaptic plasticity and excitability, suggesting that impaired eCB signaling will lead to deficits in cerebellar adjustments of ongoing behaviors and cerebellar learning. Indeed, human mutations in DAGLα are associated with neurodevelopmental disorders. In this study, we show that selective deletion of the eCB synthesizing enzyme diacylglycerol lipase alpha (Daglα) from mouse cerebellar Purkinje cells (PCs) alters motor and social behaviors, disrupts short-term synaptic plasticity in both excitatory and inhibitory synapses, and reduces Purkinje cell activity during social exploration. Our results provide the first evidence for cerebellar-specific eCB regulation of social behaviors and implicate eCB regulation of synaptic plasticity and PC activity as the neural substrates contributing to these deficits. Graphical abstract. Cerebellar anatomy, morphology of Purkinje cells, localization, density, and spontaneous activity of excitatory and inhibitory synapses are normal in cerebellar-Purkinje-cell-specific Daglα KOs. However, endocannabinoid-dependent short-term synaptic plasticity (DSE and DSI) and activity of Purkinje cells in lobe VI during social exploration are dramatically reduced, and the KO mice exhibit alterations in sensorimotor coordination, deceased social preference, and increased anxiety.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma 解密肿瘤微环境，阐明卵巢透明细胞癌的癌细胞起源

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.606821

Uma S Kamaraj, Pradeep Gautam, Terence Cheng, Tham Su Chin, Sun Kuie Tay, Tew Hong Ho, R. Nadarajah, Ronald Chin Hong Goh, Shing Lih Wong, Sangeeta Mantoo, I. Busmanis, Hu Li, Minh TN Le, Qi-Jing Li, Elaine Hsuen Lim, Y. Loh

{"title":"Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma","authors":"Uma S Kamaraj, Pradeep Gautam, Terence Cheng, Tham Su Chin, Sun Kuie Tay, Tew Hong Ho, R. Nadarajah, Ronald Chin Hong Goh, Shing Lih Wong, Sangeeta Mantoo, I. Busmanis, Hu Li, Minh TN Le, Qi-Jing Li, Elaine Hsuen Lim, Y. Loh","doi":"10.1101/2024.08.06.606821","DOIUrl":"https://doi.org/10.1101/2024.08.06.606821","url":null,"abstract":"Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC’s biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglia initially seed and later reshape amyloid plaques in Alzheimer’s disease 小胶质细胞最初为阿尔茨海默病的淀粉样蛋白斑块播下种子，后来对其进行重塑

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.606783

Nóra Baligács, Giulia Albertini, Sarah C. Borrie, L. Serneels, Clare Pridans, S. Balusu, Bart De Strooper

引用次数: 0

The spatial spread and the persistence of gene drives are affected by demographic feedbacks, density dependence and Allee effects 基因驱动因素的空间传播和持久性受到人口反馈、密度依赖性和阿利效应的影响

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.08.607064

Léna Kläy, Léo Girardin, Vincent Calvez, F. Débarre

{"title":"The spatial spread and the persistence of gene drives are affected by demographic feedbacks, density dependence and Allee effects","authors":"Léna Kläy, Léo Girardin, Vincent Calvez, F. Débarre","doi":"10.1101/2024.08.08.607064","DOIUrl":"https://doi.org/10.1101/2024.08.08.607064","url":null,"abstract":"Homing gene drive alleles bias their own transmission by converting wild-type alleles into drive alleles. If introduced in a natural population, they might fix within a relatively small number of generations, even if they are deleterious. No engineered homing gene drive organisms have been released in the wild so far, and modelling is essential to develop a clear understanding of the potential outcomes of such releases. We use deterministic models to investigate how different demographic features affect the spatial spread of a gene drive. Building on previous work, we first consider the effect of the intrinsic population growth rate on drive spread. We confirm that including demographic dynamics can change outcomes compared to a model ignoring changes in population sizes, because changes in population density can oppose the spatial spread of a drive. Secondly, we study the consequences of including an Allee effect, and find that it makes a population more prone to eradication following drive spread. Finally, we investigate the effects of the fitness component on which density dependence operates (fecundity or survival), and find that it affects the speed of drive invasion in space, and can accentuate the consequences of an Allee effect. These results confirm the importance of checking the robustness of model outcomes to changes in the underlying assumptions, especially if models are to be used for gene drive risk assessment.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PLSKO: a robust knockoff generator to control false discovery rate in omics variable selection PLSKO：用于控制 omics 变量选择中错误发现率的鲁棒山寨生成器

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.606935

Guannan Yang, E. Menkhorst, E. Dimitriadis, K. Lê Cao

{"title":"PLSKO: a robust knockoff generator to control false discovery rate in omics variable selection","authors":"Guannan Yang, E. Menkhorst, E. Dimitriadis, K. Lê Cao","doi":"10.1101/2024.08.06.606935","DOIUrl":"https://doi.org/10.1101/2024.08.06.606935","url":null,"abstract":"The knockoff framework, combined with variable selection procedure, controls false discovery rate (FDR) without the need for calculating p−values. Hence, it presents an attractive alternative to differential expression analysis of high-throughput biological data. However, current knockoff variable generators make strong assumptions or insufficient approximations that lead to FDR inflation when applied to biological data. We propose Partial Least Squares Knockoff (PLSKO), an efficient and assumption-free knockoff generator that is robust to varying types of biological omics data. We compare PLSKO with a wide range of existing methods. In simulation studies, we show that PLSKO is the only method that controls FDR with sufficient statistical power in complex non-linear cases. In semi-simulation studies based on real data, we show that PLSKO generates valid knockoff variables for different types of biological data, including RNA-seq, proteomics, metabolomics and microbiome. In preeclampsia multi-omics case studies, we combined PLSKO with Aggregation Knockoff to address the randomness of knockoffs and improve power, and show that our method is able to select variables that are biologically relevant.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MYCN inhibits TrkC-mediated differentiation in neuroblastoma cells via disruption of the PKA signalling pathway MYCN 通过破坏 PKA 信号通路抑制由 TrkC 介导的神经母细胞瘤细胞分化

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.07.606961

Stephanie Maher, Kieran Wynne, Vadim Zhernovkov, Melinda Halasz

{"title":"MYCN inhibits TrkC-mediated differentiation in neuroblastoma cells via disruption of the PKA signalling pathway","authors":"Stephanie Maher, Kieran Wynne, Vadim Zhernovkov, Melinda Halasz","doi":"10.1101/2024.08.07.606961","DOIUrl":"https://doi.org/10.1101/2024.08.07.606961","url":null,"abstract":"Neuroblastoma is a complex paediatric cancer with a spectrum of clinical outcomes ranging from spontaneous regression to aggressive metastatic disease. Low-risk patients achieve over 90% survival with no or minimal treatment, while high-risk patients face less than 50% survival despite intensive multimodal therapy. Half of the high-risk cases harbour amplification of the MYCN oncogene. In addition to MYCN status, Trk receptors have also been linked to prognosis. TrkA expression is seen with low-risk cases while TrkB expression often occurs in high-risk MYCN-amplified NB. While TrkA and TrkB are well studied in NB, the role of TrkC in neuroblastoma genesis is not clear. Therefore, this study investigates the interplay between MYCN status and NT-3/TrkC signalling in neuroblastoma. Using a panel of neuroblastoma cell lines with varying MYCN levels, we found that TrkC activation leads to neuronal differentiation of MYCN non-amplified cells, whereas it promotes proliferation of MYCN-amplified cells. Temporal phosphoproteomics revealed differential activation of the PKA pathway, which was crucial for TrkC-mediated differentiation. Manipulating the PKA pathway altered cell fate outcomes, underscoring its role. In MYCN-amplified cells, MYCN knockdown increased PKA and CREB activity, shifting the phenotype towards differentiation. Analysis of neuroblastoma patient data showed lower expression of PKA pathway genes in MYCN-amplified tumours. Additionally, miR-221, upregulated by MYCN, was identified as a suppressor of the PKA/CREB pathway. These findings highlight the context-dependent nature of NT-3/TrkC signalling influenced by MYCN; and suggest therapeutic potential in targeting the PKA pathway to induce differentiation of high-risk MYCN-amplified neuroblastoma.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Female Túngara Frogs Discriminate against the Call of Males Infected by Chytridiomycosis 雌性图恩加拉蛙辨别感染恙虫病的雄蛙的叫声

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.606873

Sofía Rodríguez-Brenes, Sylvia F. Garza, Michael J. Ryan

{"title":"Female Túngara Frogs Discriminate against the Call of Males Infected by Chytridiomycosis","authors":"Sofía Rodríguez-Brenes, Sylvia F. Garza, Michael J. Ryan","doi":"10.1101/2024.08.06.606873","DOIUrl":"https://doi.org/10.1101/2024.08.06.606873","url":null,"abstract":"Species worldwide are disappearing in the most devastating mass extinction in human history and one of the six most profound extinctions in the history of life. Amphibians are greatly affected, approximately one third of living species are threatened, and many others are extinct. One of the main causes of amphibian species extinctions and population declines is the emerging infectious disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd). Although some species are somewhat tolerant of the disease, the non-lethal effects of the infection with Bd and their short or long term consequences are poorly understood. In these species there is the potential for behavioral responses to mitigate the spread of the fungus. Here we show that in túngara frogs, infection status influences the males’ mating calls. These infection-induced changes in the quality of males’ mating calls ultimately reduce the calls’ attractiveness to females making females less likely to respond to and thus mate with infected males. More broadly, our results imply that females might avoid mating with disease-infected males by assessing the acoustic signal only, and that such recruitment of behavioral responses might potentially ameliorate some of the effects of this sixth mass extinction. Lay summary Chytridiomycosis is an amphibian disease well known for its lethal effects. Túngara frogs are infected in nature, but seem to be resistant to the disease. Here we show that chytridiomycosis has non-lethal behavioral effects on túngara frogs. Females discriminate against infected males by assessing only their acoustic signal. The mating call of a male that is not infected with the disease is more attractive to females than the call of that same male when he is infected.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sexual receptivity increases in synchrony with the ovulatory cycle in female medaka 雌性青鳉的性接受能力与排卵周期同步增长

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.606788

Soma Tomihara, Rinko Shimomai, Mikoto Nakajo, Yoshitaka Oka, Chie Umatani

引用次数: 0

Phylogenomic prediction of interaction networks in the presence of gene duplication 基因重复情况下相互作用网络的系统发生学预测

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.606904

Tony C Gatts, Chris deRoux, Linnea E Lane, Monica Berggren, Elizabeth A Rehmann, Emily N Zak, Trinity Bartel, Luna L’Argent, Daniel B. Sloan, Evan S. Forsythe

{"title":"Phylogenomic prediction of interaction networks in the presence of gene duplication","authors":"Tony C Gatts, Chris deRoux, Linnea E Lane, Monica Berggren, Elizabeth A Rehmann, Emily N Zak, Trinity Bartel, Luna L’Argent, Daniel B. Sloan, Evan S. Forsythe","doi":"10.1101/2024.08.06.606904","DOIUrl":"https://doi.org/10.1101/2024.08.06.606904","url":null,"abstract":"Assigning gene function from genome sequences is a rate-limiting step in molecular biology research. A protein’s position within an interaction network can potentially provide insights into its molecular mechanisms. Phylogenetic analyses of evolutionary rate covariation (ERC) have been shown to be effective for large-scale prediction of functional interactions from protein sequence data. However, gene duplication, gene loss, and other sources of phylogenetic incongruence are barriers for analyzing ERC on a genome-wide basis. Here, we developed ERCnet, a bioinformatic program designed to overcome these challenges, facilitating efficient all-vs-all ERC analyses for large protein sequence datasets. We compiled a sample set of 35 angiosperm genomes to test the performance of ERCnet, including its sensitivity to user-defined analysis parameters such as input dataset size, branch-length measurement strategy, and significance threshold for defining ERC hits. We find that our novel ‘branch-by-branch’ length measurements outperforms ‘root-to-tip’ approaches in most cases, offering a valuable new strategy for performing ERC even in the presence of extensive gene duplication. Further, we demonstrate that the number of genomes and the species composition both have profound effects on the genes that are predicted to interact. Our systematic exploration of the performance of ERCnet provides a roadmap for design of future ERC analyses to predict functional interactions in a wide array of genomic datasets. ERCnet code is freely available at https://github.com/EvanForsythe/ERCnet.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Infants and adults neurally represent the perspective of others like their own perception 婴儿和成人在神经上将他人的视角视为自己的视角

bioRxiv Pub Date : 2024-08-08 DOI: 10.1101/2024.08.06.605501

Anna-Lena Tebbe, Katrin Rothmaler, Moritz Köster, Charlotte Grosse Wiesmann

引用次数: 0